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                        <div class="mt f24 font-m">Paracetamol </div>
                        <div class="items">
                            <div class="i"><a href="#p1">Physico-Chemical Properties</a></div>
                            <div class="i"><a href="#p2">Pharmacodynamics</a></div>
                            <div class="i"><a href="#p3">Mechanism of action</a></div>
                            <div class="i"><a href="#p4">Indication</a></div>
                            <div class="i"><a href="#p5">Objective and Search Strategy</a></div>
                            <div class="i"><a href="#p6">Hazard Identified</a></div>
                            <div class="i"><a href="#p7">Critical Effects</a></div>
                            <div class="i"><a href="#p8">Point of Departure</a></div>
                            <div class="i"><a href="#p9">Uncertainty Factors</a></div>
                            <div class="i"><a href="#p10">PDE Calculation</a></div>
                            <div class="i"><a href="#p11">References</a></div>
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                    <div class="dt f36 font-m">Paracetamol (Oral)</div>
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                        <div class="bt f24 font-m">Physico-Chemical Properties</div>
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                            <div class="li flex">
                                <div class="ll font-m">IUPAC Name </div>
                                <div class="lr">{{dataInfo.IUPAC_name}}</div>
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                                <div class="ll font-m">Description</div>
                                <div class="lr toggleML">
                                    <div class="hid">
                                        Abacavir is a 2,6-diaminopurine that is (1S)-cyclopent-2-en-1-ylmethanol in
                                        which the pro-R hydrogen at the 4-position is substituted by a
                                        2-amino-6-(cyclopropylamino)-9H-purin-9-yl group.
                                        <br>
                                        A nucleoside analogue reverse transcriptase inhibitor (NRTI) with
                                        antiretroviral activity against HIV, it is used (particularly as the
                                        sulfate) with other antiretrovirals in combination therapy of HIV infection.
                                        <br>
                                        It has a role as a HIV-1 reverse transcriptase inhibitor, an antiviral drug
                                        and a drug allergen.
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                                <div class="ll font-m">Synonyms</div>
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                                    <div class="p">
                                        Azithromycin<br>
                                        Zithromax<br>
                                        Abacavir<br>
                                        136470-78-5<br>
                                        Ziagen<br>
                                        Abacavir sulfate<br>
                                        Abacavir [INN]<br>
                                        1592U89<br>
                                        (1S,4R)-4-[2-Amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol<br>
                                        Abacavir (INN)<br>
                                        CHEBI:421707<br>
                                        WR2TIP26VS<br>
                                        ((1S,4R)-4-(2-amino-6-(cyclopropylamino)-9H-purin-9-yl)cyclopent-2-en-1-yl)methanol<br>
                                        MFCD00903850<br>
                                        [(1S,4R)-4-[2-amino-6-(cyclopropylamino)purin-9-yl]cyclopent-2-en-1-yl]methanol<br>
                                        {(1S-cis)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl}methanol<br>
                                        2-Cyclopentene-1-methanol<br>
                                        4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-<br>
                                        (1S,4R)-<br>
                                        NSC-742406<br>
                                        [(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl]methanol<br>
                                        [(1s,4r)-4-[2-amino-6-(cyclopropylamino)purin-9-yl]-1-cyclopent-2-enyl]methanol<br>
                                        Avacavir<br>
                                        ABC<br>
                                        136777-48-5
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                                </div>
                            </div>
                            <div class="li flex">
                                <div class="ll font-m">Molecular Weight</div>
                                <div class="lr">C15H12N20</div>
                            </div>
                            <div class="li flex">
                                <div class="ll font-m">CAS Number</div>
                                <div class="lr">298-46-4</div>
                            </div>
                            <div class="li flex">
                                <div class="ll font-m">Inchl Key </div>
                                <div class="lr">FFGPTBGBLSHEPO-UHFFFAOYSA-N </div>
                            </div>
                            <div class="li flex">
                                <div class="ll font-m">Smiles</div>
                                <div class="lr">C1=CC=C2C(=C1)C=CC3=CC=CC=C3N2C(=ON</div>
                            </div>
                            <div class="li flex">
                                <div class="ll font-m">ATC Code</div>
                                <div class="lr">N02BE01</div>
                            </div>
                            <div class="li flex">
                                <div class="ll font-m">Pharmacotherapeutic Group</div>
                                <div class="lr">Analgesics,Antipyretics</div>
                            </div>
                            <div class="li flex">
                                <div class="ll font-m">Appearance</div>
                                <div class="lr">It is of white color in the form of solid crystals.</div>
                            </div>
                            <div class="li flex">
                                <div class="ll font-m">Solubility</div>
                                <div class="lr">It is soluble in water,very slightly soluble in cold water but
                                    greater solubility in hot water.</div>
                            </div>
                            <div class="li flex">
                                <div class="ll font-m">Molecular Structure</div>
                                <div class="lr">
                                    <img src="/uploadfiles/detail.png" alt="">
                                </div>
                            </div>
                        </div>
                    </div>
                </div>
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                        <div id="p2" class="pos"></div>
                        <div class="bt f24 font-m">Pharmacodynamics</div>
                        <div class="btxt f16">
                            Animal and clinical studies have determined that acetaminophen has both antipyretic and
                            analgesic effects. <br>
                            This drug has been shown to lack anti-inflammatory effects.As opposed to the salicylate drug
                            class,acetaminophen does not disrupt tubular secretion of uric acid and does not affect
                            acid-base balance if taken at the recommended doses.23 Acetaminophen does not disrupt
                            hemostasis and does not have inhibitory activities against platelet aggregation.Label,23
                            Allergic reactions are rare occurrences following acetaminophen use.23
                        </div>
                    </div>
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                        <div class="bt f24 font-m">Mechanism of action</div>
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                            According to its FDA labeling,acetaminophen's exact mechanism of action has not been fully
                            establishedLabel despite this,it is often categorized alongside NSAlDs (nonsteroidal
                            anti-inflammatory drugs)due to its ability to inhibit the cyclooxygenase (COX)pathways.14 It
                            is thought to exert central actions which ultimately lead to the alleviation of pain
                            symptoms.14One theory is that acetaminophen increases the pain threshold by inhibiting two
                            isoforms of cyclooxygenase,COX-1 and COX-2,which are involved in prostaglandin
                            (PG)synthesis.Prostaglandins are responsible for eliciting pain sensations.13 Acetaminophen
                            does not inhibit cyclooxygenase in peripheral tissues and,therefore,has no peripheral
                            anti-inflammatory effects.Though acetylsalicylic acid (aspirin)is an irreversible inhibitor
                            of COX and directly blocks the active site of this enzyme,studies have shown that
                            acetaminophen (paracetamol)blocks COX
                            indirectly.24 Studies also suggest that acetaminophen selectively blocks a variant type of
                            the COX enzyme that is unique from the known variants COX-1 and COX-2.6 This enzyme has been
                            referred to as COX-3.The antipyretic actions of acetaminophen are likely attributed to
                            direct action on heat-regulating centers in the brain,resulting in peripheral
                            vasodilation,sweating,and loss of body heat.24 The exact mechanism of action of this drug is
                            not fully understood at this time. but future research may contribute to deeper knowledge.24

                        </div>
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                        <div class="bt f24 font-m">Indication</div>
                        <div class="btxt f16">
                            In general,acetaminophen is used for the treatment of mild to moderate pain and reduction of
                            fever.23 It is available over the counter in various forms,the most common being oral forms.
                            Acetaminophen injection is indicated for the management of mild to moderate pain,the
                            management of moderate to severe pain with adjunctive opioid analgesics,and the reduction of
                            fever. Label Because of its low risk of causing allergic reactions,this drug can be
                            administered in patients who are intolerant to salicylates and those with allergic
                            tendencies,including bronchial asthmatics.23 Specific dosing guidelines should be followed
                            when administering acetaminophen to children.18

                        </div>
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                        <div class="bt f24 font-m">Objective and Search Strategy</div>
                        <div class="btxt f16">
                            At present,pharmaceutical companies are investing significant effort to assess and control
                            crosscontamination risk of drug products that are manufactured in the shared production
                            facilities(2). Determination of health-based exposure limits for a residual active substance
                            through the derivation of a safe threshold value is employed to identify the risk posed.The
                            derivation of threshold value like permitted daily exposure(PDE)or threshold of
                            toxicological concern is used to determine the risk of the active pharmaceutical
                            substance.For determination of PDE all the available pharmacological and toxicological data
                            including both non-clinical and clinical data
                            should be evaluated.This involves hazard identification by reviewing all relevant data,
                            identification of critical effects,determination of NOAEL of the findings that are
                            considered to be critical effects.
                            In this document,a summary of pharmacological,pharmacokinetics and toxicity data of
                            paracetamol has been presented based on the published data.The data were extracted from Pub
                            chem,Drug bank and FDA.

                        </div>
                    </div>
                    <div class="dblock">
                        <div id="p6" class="pos"></div>
                        <div class="bt flex">
                            <div class="tl f24 font-m">Hazard Identified</div>
                            <div class="tr"><NuxtLink to="/APIs/ToxicityData">More Details</NuxtLink></div>
                        </div>
                        <div class="btxt f16">
                            <div class="li flex">
                                <div class="ll">Carcinogen </div>
                                <div class="lc">NO</div>
                                <div class="lr">Carcinogenic studies conducted in mice and rats did not revealed any
                                    carcinogenic potential of paracetamol</div>
                            </div>
                            <div class="li flex">
                                <div class="ll">Genotoxicant</div>
                                <div class="lc">NO</div>
                                <div class="lr">Paracetamol doesn't produce mutagenicity in Ames test conducted in
                                    S.typhimurium strains but it produced sister chromatid exchanges and chromosomal
                                    aberrations in Chinese Hamster ovary cells,however it is highly unlikely that
                                    paracetamol can produce mutagenic effects in humans.</div>
                            </div>
                            <div class="li flex">
                                <div class="ll">Reproductive/Developmental Toxicant </div>
                                <div class="lc">NO</div>
                                <div class="lr">Reproductive studies were conducted in rats and rabbits.Testicular
                                    atrophy,fertility impairment and fetotoxicity was observed in rats at higher doses
                                    and reductions in fertility and neonatal survival, sperm abnormalities were observed
                                    in mice.</div>
                            </div>
                            <div class="li flex">
                                <div class="ll">Highly Sensitizing Potential</div>
                                <div class="lc">UNKNOWN</div>
                                <div class="lr">There weren't any positive indicators in local tolerance study conducted
                                    in rabbits and in skin sensitization study performed in guinea pigs.</div>
                            </div>
                        </div>
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                        <div id="p7" class="pos"></div>
                        <div class="bt flex">
                            <div class="tl f24 font-m">
                                Critical Effects <br>
                                hepatotoxicity and nephrotoxicity
                            </div>
                            <div class="tr"><NuxtLink to="/APIs/PDE">More Details</NuxtLink></div>
                        </div>
                        <div class="btxt f16">
                            <div class="li flex">
                                <div class="ll">Non-clinical</div>
                                <div class="lr">The critical or lead effects of paracetamol were reported to be
                                    hepatotoxicity and nephrotoxicity[<a href="">1</a>].</div>
                            </div>
                            <div class="li flex">
                                <div class="ll">Clinical</div>
                                <div class="lr">Paracetamol is used in the management of mild to moderate pain and
                                    reduction of fever.It is also used in the management of moderate to severe pain with
                                    adjunctive opioid analgesics.The most common adverse effects associated with
                                    paracetamol wereincreased aspartate aminotransferase,nausea,vomiting,abdominal
                                    pain,diarrhea,constipation,dyspepsia,enlarged
                                    abdomen,insomnia,rash,pruritus,insomnia,anxiety,fatigue.Administration of
                                    acetaminophen in doses higher than recommended may result in hepatic injury.</div>
                            </div>
                        </div>
                    </div>
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                            <div class="tl f24 font-m">
                                Point of Departure<br>
                                400 mg/kg/day
                            </div>
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                        <div class="btxt f16">
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                                <div class="lr">
                                    Repeated dose toxicity studies were conducted in rodents up to 13 weeks.From the
                                    availabledata,value of 400 mg/kg/day is selected as NOAEL for the derivation of
                                    final PDE value from rat's4-week. The rationale behind selection of this study as it
                                    was conducted by intravenous route and the oralbioavailability is 88%and is
                                    approximately equal to intravenous route.Moreover,all doses welltolerated and no
                                    histological liver changes or changes in liver enzymes or bilirubin,and there areno
                                    indications of renal damage.
                                </div>
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                        <div id="p9" class="pos"></div>
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                            <div class="tl f24 font-m">
                                Uncertainty Factors
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                        </div>
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                            <table>
                                <tbody>
                                    <tr>
                                        <th class="f18 font-m">Factors</th>
                                        <th class="f18 font-m">Value</th>
                                        <th class="f18 font-m">Rationale</th>
                                    </tr>
                                    <tr>
                                        <td class="f18 font-m">F1</td>
                                        <td class="f18 font-m">5</td>
                                        <td>For extrapolation from rats to humans.</td>
                                    </tr>
                                    <tr>
                                        <td class="f18 font-m">F2</td>
                                        <td class="f18 font-m">10</td>
                                        <td>Conventionally used to allow for differences between individuals in the
                                            human population.</td>
                                    </tr>
                                    <tr>
                                        <td class="f18 font-m">F3</td>
                                        <td class="f18 font-m">10</td>
                                        <td>For selection of 4-week toxicity study in rats.</td>
                                    </tr>
                                    <tr>
                                        <td class="f18 font-m">F4</td>
                                        <td class="f18 font-m">5</td>
                                        <td>Based on the hepatotoxicity.</td>
                                    </tr>
                                    <tr>
                                        <td class="f18 font-m">F5</td>
                                        <td class="f18 font-m">1</td>
                                        <td>Selection of LOAEL dose.</td>
                                    </tr>
                                    <tr>
                                        <td class="f18 font-m">α</td>
                                        <td class="f18 font-m">1</td>
                                        <td>A factor of 1 is applied.</td>
                                    </tr>
                                </tbody>
                            </table>
                        </div>
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                        <div id="p10" class="pos"></div>
                        <div class="bt flex">
                            <div class="tl f24 font-m">
                                PDE Calculation
                            </div>
                        </div>
                        <div class="btxt f16">
                            <div class="li fle">
                                <div class="lr">
                                    <img src="/uploadfiles/detail2.png" alt="">
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                        <div class="bt f24 font-m">References</div>
                        <div class="btxt f16">
                            <ul>
                                <li>Forrest JA,Clements JA,Prescott LF:Clinical pharmacokinetics of paracetamol.Clin
                                    Pharmacokinet.1982 Mar-Apr;7(2):93-107.[<a href="">Article</a>]</li>
                                <li>Ricciotti E,FitzGerald GA:Prostaglandins and inflammation.Arterioscler Thromb Vasc
                                    Biol. 2011May;31(5):986-1000.doi: 10.1161/ATVBAHA.110. 207449.[<a
                                        href="">Article</a>]</li>
                                <li>Valerie Gerriets;Thomas M.Nappe (2019).Acetaminophen.StatPearls publishing.</li>
                                <li>Acetaminophen tablet,DailyMed [<a href="">Link</a>]</li>
                                <li>Acetaminophen effervescent tablets,Cleveland Clinic [<a href="">Link</a>]</li>
                                <li>FDA safety communication:FDA has reviewed possible risks of pain medicine use during
                                    pregnancy [<a href="">Link</a>]</li>
                                <li>U.S.National Medical Library:MedlinePlus-Acetaminophen dosing for children [<a
                                        href="">Link</a>]</li>
                                <li>FDA consumer health information:Acetaminophen [<a href="">Link</a>]</li>
                                <li>FDA Acetaminophen Information [<a href="">Link</a>]</li>
                                <li>Using Acetaminophen and Nonsteroidal Anti-inflammatory Drugs Safely [<a
                                        href="">Link</a>]</li>
                                <li>FDA Approved Drug Products:Acetaminophen solution for intravenous injection [<a
                                        href="">Link</a>]</li>
                                <li>Acetaminophen monograph,suppository [<a href="">File</a>]</li>
                            </ul>
                        </div>
                    </div>
                </div>
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